In a large number of situations, it is desirable to be able to precisely control the flow rate of a liquid. Often, it is also desirable to modify the flow rate over time. For example, the therapeutic effect of many biologically active agents is critically dependent upon their circulating concentration in a patient. The therapeutic concentration range may be quite limited, with lower concentrations being ineffective and higher concentrations producing undesirable toxic effects.
Electrorelease is known in the art as a useful technique for electrochemically controlling the delivery of a chemical or drug. The delivery process can be controlled by switching the electrorelease system on and off, or by adjusting the rate of release. Electrorelease systems for small molecules are generally based on chemical entrapment of the molecule in a polymeric support.
Journal of the Electrochemical Society 137: 3789-3793 (1990) and references therein describe an electrorelease system for macromolecules based on microporous membranes. The molecule to be released is physically entrapped behind a composite membrane consisting of a microporous support membrane covered by a non-porous barrier layer. Release is initiated by electrochemically dissolving or disrupting the barrier layer. A thin metallic electrode, which does not seal the membrane's pores, is sandwiched between the microporous membrane and the non-porous barrier layer. The electrorelease rate is controlled by the number of pores which are electrochemically opened. The rate is modulated by limiting the amount of current passed during oxidation of the barrier layer or by separating the microporous membrane into individual electrorelease zones.
While it is possible to increase the electrorelease rate by opening more pores, the rate may not be decreased because the pores, once opened, cannot be closed. The resolution with which the release rate may be controlled is limited by the size of the separate electrorelease zones which may be constructed on the membrane surface and the number of pores within each zone.
It is therefore an object of the present invention to provide an improved electrorelease system for macromolecules which allows the electrorelease rate to be reduced or stopped.
It is a further object to provide an improved electrorelease system which has increased flow rate resolution.